Herpes viruses, particularly the ubiquitous herpes simplex viruses, have a complex pathogenesis, and have long been recognized to be responsible for a variety of syndromes in man. Our previous work was aimed at an initial definition of this pathogenesis. Most importantly, we showed that experimental latent infections could be established in the nervous system. We propose to continue and extend these pathogenetic studies in experimental systems. The principal models used will be Herpes simplex virus and Murine cytomegalovirus in genetically defined strains of mice. Here, using immunologic, virologic, histologic, and biochemical methods, we will study the physiological basis for latency and reactivation. In neurophysiologic experiments, a comprehensive, pioneering investigation concerning the effect of acute, latent and reactivating herpes simplex infections on electrical activities and synaptic transmission of neurons will be initiated. Finally, with the aid of biochemical techniques, mechanisms operative in the genetic regulation of herpes simplex virus in cell cultures will be delineated.